Composition and Structure - Lipid Nanoparticles: Production, Characterization and Stability - page 16

Fig. 2.1 Drug incorporation models of solid lipid nanoparticles. a Drug-enriched shell model.
b Drug-enriched core model. c Solid solution (homogenous matrix) model
Fig. 2.2 Drug incorporation models of nanostructured lipid carriers. a Type I or the imperfect
crystal type NLC. b Type II or the multiple type NLC. c Type III or the amorphous type NLC
be explained by a lipid precipitation mechanism that occurs during production
and by repartitioning of the drug that occurs during the cooling stage. After hot
homogenization, each droplet is a mixture of melted lipid and drug. Rapid cool-
ing accelerates lipid precipitation at the core with a concomitant increase in drug
concentration in the outer liquid lipid. Complete cooling leads to precipitation of
a drug-enriched shell. This structural model is suitable for incorporation of drugs
that are released as a burst. Such a rapid release is highly desirable for dermato-
logical SLN formulations that require increased drug penetration, in addition to
the occlusive effect of the SLN (Muchow et al. 2008 ). The controlled release of
clotrimazole from a topical SLN formulation was due to its drug-enriched shell
structure (Souto et al. 2004 ).
The solubility of the drug in the surfactant-water mixture at elevated tempera-
tures is another factor that can influence precipitation of drug in the shell. During
the hot homogenization process, drug partially moves out of the lipid core due to
its increased solubility in the surfactant solution. However, solubility of the drug
in the surfactant solution decreases as the dispersion is cooled. This leads to drug
enrichment in the shell, in cases where lipid core solidification has already started
(Muchow et al. 2008 ).